TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18949	57070;57071;57072	chr2:178598865;178598864;178598863	chr2:179463592;179463591;179463590
N2AB	17308	52147;52148;52149	chr2:178598865;178598864;178598863	chr2:179463592;179463591;179463590
N2A	16381	49366;49367;49368	chr2:178598865;178598864;178598863	chr2:179463592;179463591;179463590
N2B	9884	29875;29876;29877	chr2:178598865;178598864;178598863	chr2:179463592;179463591;179463590
Novex-1	10009	30250;30251;30252	chr2:178598865;178598864;178598863	chr2:179463592;179463591;179463590
Novex-2	10076	30451;30452;30453	chr2:178598865;178598864;178598863	chr2:179463592;179463591;179463590
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-25
• Domain position: 66
• Structural Position: 92
• Q(SASA): 0.3912
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/E	None	None	0.454	N	0.511	0.184	0.209622950755	gnomAD-4.0.0	1.5922E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8599E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.5626	ambiguous	0.5156	ambiguous	-0.501	Destabilizing	0.688	D	0.529	neutral	None	None	None	None	I
K/C	0.7883	likely_pathogenic	0.7579	pathogenic	-0.548	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	I
K/D	0.7698	likely_pathogenic	0.7132	pathogenic	0.189	Stabilizing	0.007	N	0.299	neutral	None	None	None	None	I
K/E	0.3882	ambiguous	0.3376	benign	0.257	Stabilizing	0.454	N	0.511	neutral	N	0.460721364	None	None	I
K/F	0.9059	likely_pathogenic	0.8766	pathogenic	-0.474	Destabilizing	0.974	D	0.569	neutral	None	None	None	None	I
K/G	0.7836	likely_pathogenic	0.739	pathogenic	-0.796	Destabilizing	0.842	D	0.586	neutral	None	None	None	None	I
K/H	0.37	ambiguous	0.3436	ambiguous	-1.139	Destabilizing	0.974	D	0.565	neutral	None	None	None	None	I
K/I	0.4635	ambiguous	0.4374	ambiguous	0.227	Stabilizing	0.111	N	0.503	neutral	N	0.461510798	None	None	I
K/L	0.5186	ambiguous	0.5073	ambiguous	0.227	Stabilizing	0.525	D	0.553	neutral	None	None	None	None	I
K/M	0.3849	ambiguous	0.3824	ambiguous	0.141	Stabilizing	0.974	D	0.565	neutral	None	None	None	None	I
K/N	0.583	likely_pathogenic	0.5854	pathogenic	-0.188	Destabilizing	0.801	D	0.546	neutral	N	0.466089899	None	None	I
K/P	0.7533	likely_pathogenic	0.7496	pathogenic	0.014	Stabilizing	0.974	D	0.627	neutral	None	None	None	None	I
K/Q	0.1934	likely_benign	0.1962	benign	-0.321	Destabilizing	0.051	N	0.335	neutral	N	0.486291812	None	None	I
K/R	0.0854	likely_benign	0.0874	benign	-0.364	Destabilizing	0.012	N	0.297	neutral	N	0.399904979	None	None	I
K/S	0.6175	likely_pathogenic	0.5895	pathogenic	-0.875	Destabilizing	0.842	D	0.543	neutral	None	None	None	None	I
K/T	0.2147	likely_benign	0.2146	benign	-0.613	Destabilizing	0.801	D	0.579	neutral	N	0.386988823	None	None	I
K/V	0.3838	ambiguous	0.3723	ambiguous	0.014	Stabilizing	0.728	D	0.587	neutral	None	None	None	None	I
K/W	0.8845	likely_pathogenic	0.8613	pathogenic	-0.344	Destabilizing	0.998	D	0.598	neutral	None	None	None	None	I
K/Y	0.8004	likely_pathogenic	0.7605	pathogenic	-0.034	Destabilizing	0.991	D	0.585	neutral	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.